ArticleNature communications2018
Argininosuccinic aciduria fosters neuronal nitrosative stress reversed by Asl gene transfer.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- Clinical, biochemical and genetic characteristics of patients with argininosuccinate lyase deficiency from a single center cohort in China.Orphanet journal of rare diseases · 2025Article
- Identification of the potential pathogenicity of a VUS in the ASL gene associated with argininosuccinic aciduria in an Iranian family.Molecular biology reports · 2025Article
- Recent developments in translational imaging of in vivo gene therapy outcomes.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Gene therapy prevents hepatic mitochondrial dysfunction in murine deoxyguanosine kinase deficiency.Molecular therapy. Methods & clinical development · 2025Article
- Positive Clinical, Neuropsychological, and Metabolic Impact of Liver Transplantation in Patients With Argininosuccinate Lyase Deficiency.Journal of inherited metabolic disease · 2025Article
- The incidence of movement disorder increases with age and contrasts with subtle and limited neuroimaging abnormalities in argininosuccinic aciduria.Journal of inherited metabolic disease · 2024Article
- mRNA therapy corrects defective glutathione metabolism and restores ureagenesis in preclinical argininosuccinic aciduria.Science translational medicine · 2024Article
- Gene therapy for urea cycle defects: An update from historical perspectives to future prospects.Journal of inherited metabolic disease · 2024Review
- ASL mRNA-LNP Therapeutic for the Treatment of Argininosuccinic Aciduria Enables Survival Benefit in a Mouse Model.Biomedicines · 2023Article
- Gene Therapy in Combination with Nitrogen Scavenger Pretreatment Corrects Biochemical and Behavioral Abnormalities of Infant Citrullinemia Type 1 Mice.International journal of molecular sciences · 2022Article
- Modelling urea cycle disorders using iPSCs.NPJ Regenerative medicine · 2022Review
- Neonatal gene therapy achieves sustained disease rescue of maple syrup urine disease in mice.Nature communications · 2022Article
- HBM4EU Chromates Study: Urinary Metabolomics Study of Workers Exposed to Hexavalent Chromium.Metabolites · 2022Article
- CRISPR-Mediated Genomic Addition to CPS1 Deficient iPSCs is Insufficient to Restore Nitrogen Homeostasis.The Yale journal of biology and medicine · 2021Article
- Late-onset argininosuccinic aciduria in a 72-year-old man presenting with fatal hyperammonemia.JIMD reports · 2021Article
- ASL expression in ALDH1A1Human genetics · 2021Article
- Identification of rare variants causing urea cycle disorders: A clinical, genetic, and biophysical study.Journal of cellular and molecular medicine · 2021Article
- Beclin-1-mediated activation of autophagy improves proximal and distal urea cycle disorders.EMBO molecular medicine · 2021Article
- Gene therapy for inherited metabolic diseases.Journal of mother and child · 2020Review
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
Abstract
Argininosuccinate lyase (ASL) belongs to the hepatic urea cycle detoxifying ammonia, and the citrulline-nitric oxide (NO) cycle producing NO. ASL-deficient patients present argininosuccinic aciduria characterised by hyperammonaemia, multiorgan disease and neurocognitive impairment despite treatment aiming to normalise ammonaemia without considering NO imbalance. Here we show that cerebral disease in argininosuccinic aciduria involves neuronal oxidative/nitrosative stress independent of hyperammonaemia. Intravenous injection of AAV8 vector into adult or neonatal ASL-deficient mice demonstrates long-term correction of the hepatic urea cycle and the cerebral citrulline-NO cycle, respectively. Cerebral disease persists if ammonaemia only is normalised but is dramatically reduced after correction of both ammonaemia and neuronal ASL activity. This correlates with behavioural improvement and reduced cortical cell death. Thus, neuronal oxidative/nitrosative stress is a distinct pathophysiological mechanism from hyperammonaemia. Disease amelioration by simultaneous brain and liver gene transfer with one vector, to treat both metabolic pathways, provides new hope for hepatocerebral metabolic diseases.
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